Unknown,Transcriptomics,Genomics,Proteomics

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The genetic landscape of mutations in Burkitt lymphoma


ABSTRACT: Burkitt lymphoma is characterized by deregulation of MYC, but the contribution of other genetic mutations to the disease is largely unknown. Here, we describe the first completely sequenced genome from a Burkitt lymphoma tumor and germline DNA from the same affected individual. We further sequenced the exomes of 59 Burkitt lymphoma tumors and compared them to sequenced exomes from 94 diffuse large B-cell lymphoma (DLBCL) tumors. We identified 70 genes that were recurrently mutated in Burkitt lymphomas, including ID3, GNA13, RET, PIK3R1 and the SWI/SNF genes ARID1A and SMARCA4. Our data implicate a number of genes in cancer for the first time, including CCT6B, SALL3, FTCD and PC. ID3 mutations occurred in 34% of Burkitt lymphomas and not in DLBCLs. We show experimentally that ID3 mutations promote cell cycle progression and proliferation. Our work thus elucidates commonly occurring gene-coding mutations in Burkitt lymphoma and implicates ID3 as a new tumor suppressor gene. Gene expression profiling on 21 Burkitt lymphomas was performed using standard Affymetrix protocols as described previously. Briefly, 1 μg of total RNA was reverse transcribed, using oligo(dT) primer to synthesize cDNA. T7 primer was used for in vitro transcription, resulting in labeled cRNA, which was fragmented and hybridized to Affymetrix Whole-Genome Gene 1.0 ST microarrays. Microarrays were washed and scanned, and the data were normalized as described previously.

ORGANISM(S): Homo sapiens

SUBMITTER: Dereje Jima 

PROVIDER: E-GEOD-48435 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Deep sequencing of the small RNA transcriptome of normal and malignant human B cells identifies hundreds of novel microRNAs.

Jima Dereje D DD   Zhang Jenny J   Jacobs Cassandra C   Richards Kristy L KL   Dunphy Cherie H CH   Choi William W L WW   Au Wing Yan WY   Srivastava Gopesh G   Czader Magdalena B MB   Rizzieri David A DA   Lagoo Anand S AS   Lugar Patricia L PL   Mann Karen P KP   Flowers Christopher R CR   Bernal-Mizrachi Leon L   Naresh Kikkeri N KN   Evens Andrew M AM   Gordon Leo I LI   Luftig Micah M   Friedman Daphne R DR   Weinberg J Brice JB   Thompson Michael A MA   Gill Javed I JI   Liu Qingquan Q   How Tam T   Grubor Vladimir V   Gao Yuan Y   Patel Amee A   Wu Han H   Zhu Jun J   Blobe Gerard C GC   Lipsky Peter E PE   Chadburn Amy A   Dave Sandeep S SS  

Blood 20100823 23


A role for microRNA (miRNA) has been recognized in nearly every biologic system examined thus far. A complete delineation of their role must be preceded by the identification of all miRNAs present in any system. We elucidated the complete small RNA transcriptome of normal and malignant B cells through deep sequencing of 31 normal and malignant human B-cell samples that comprise the spectrum of B-cell differentiation and common malignant phenotypes. We identified the expression of 333 known miRNA  ...[more]

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